In the field of medical imaging the measurement of radiotracer distributions within a body is used to indicate the functioning of various biological processes. The body may be for example a human or animal or other organism, and the radiotracer may be a chemical compound that is preferentially uptaken by particular organs in the body. In order to measure the spatial distribution of the radiotracer, tomographic imaging such as PET and SPECT is typically used, resulting in high accuracy three-dimensional images of the radiotracer. The images may further be segmented into compartments, such as organs, subsections of organs, or tumours, the images being subsequently processed to compute the total uptake within a particular compartment. In order to determine changes in the accumulation of the radiotracer over time, multiple such three-dimensional images may be generated over the course of a period of time. Subsequently such images may be used by a physician to assist in the diagnosis of a condition or in the planning of medical treatments. By computing the uptake within a compartment at different points in time the biological functioning of a particular compartment can be determined. Furthermore the radiotracer may be used in a treatment planning step wherein the activity and distribution of the radiotracer are indicative of the activity of a radioactive therapy agent that is used to target a cancer or other malignancy. By measuring the evolution of the spatial activity of the radiotracer and computing the activity for particular compartments, a time activity curve, or TAC can be generated for each compartment and the necessary dose of radioactive therapy agent that is subsequently administered to the body during a treatment step can be determined. A TAC may further be numerically integrated to yield the area under the curve. This reflects the total number of radioactive decay events in that compartment which can be used to estimate the radiation dose.
Three-dimensional imaging of the distribution of such a radiotracer using tomographic methods yields high quality images which can be used to compute low-error TACs. However this is a time consuming exercise since the patient must typically be scanned in order to build-up the three-dimensional image from multiple slices through the body. Further, such time-consuming measurements are subject to changes in activity and radiotracer distribution during the course of the measurement which leads to measurement inaccuracies.
In seeking to resolve such inadequacies, various approaches have been made to replace some of the tomographic imaging steps outlined above with planar imaging steps, also known as scintigraphies. Scintigraphies have a shorter acquisition time and require less complex and less expensive equipment, and the use of such two-dimensional imaging equipment further reduces the resource demand for three-dimensional imaging equipment. The combination of three- and two-dimensional images is then used to determine the compartment radiotracer distribution at different points in time, and may be presented for example through a TAC. In the publication “Comparison of conventional, model-based quantitative planar, and quantitative SPECT image processing methods for organ activity estimation using In-111 agents, IOP Publishing, Phys Med Biol. 51 (2006) 3967-3981”, He and Frey report on a technique named QPLANAR that merges the advantages of fast 2D imaging with additional 3D imaging. In QPLANAR the authors use a three dimensional CT image and a planar scintigraphy as the starting point. A CT image is a three dimensional image describing the structure within an imaging volume and comprises a set of voxels or smaller three-dimensional volumes. In QPLANAR, the CT image serves as a three-dimensional reference structure of the body being imaged, from which the activity resulting from homogeneous compartment radiotracer activities is determined in the plane of the planar scintigraphy imaging system. The CT image is segmented into separate compartments; thus each voxel in the imaging volume is assigned to a particular compartment. The radiotracer activity in each compartment is represented by the product of a scaling factor and a normalised, homogeneous “basis function”; a three-dimensional matrix wherein each element represents the radiotracer activity of a voxel within the compartment. In QPLANAR it is assumed that each compartment has a homogeneous radiotracer activity; thus all voxels have the same radiotracer activity and consequently each compartment is described with a single basis function. Subsequently a projection model is used to determine the activity of the homogeneous compartment activity of radiotracer when projected onto a two-dimensional plane which corresponds to the position of the two-dimensional scintigraphy. Each compartment's basis function is therefore projected onto this plane to yield one projected basis function per compartment. The planar projection of the segmented compartments is then rigidly co-registered to the scintigraphy to assure spatial correspondence between the projection and the scintigraphy. Finally, initial estimates of the scaling factors in each compartment, such as an organ, are adjusted until a best fit is obtained between the measured activity or intensity in the scintigraphy and that modelled by the projected basis function. The best fit yields an approximation to the radiotracer activity in each compartment. By measuring several such scintigraphies over time and fitting the activities in each compartment at each time point, the desired compartment activity can be estimated at the time of each scintigraphy.
The QPLANAR approach was taken one stage further in the publication “EQPLANAR: a maximum likelihood method for accurate organ activity estimation from whole body planar projections. IOP Publishing, Phys. Med. Biol. 56 (2011) 5503-5524” by Song et al which allowed for compartment-independent registration. The optimisation process in this publication is formulated such that it not only finds the most likely homogeneous organ-independent activities, but also the most likely organ shifts which may have occurred between the acquisition of the CT image and the planar scintigraphy.
The QPLANAR approach was taken one stage closer to clinical application in the publication “Activity quantification combining conjugate-view planar scintigraphies and SPECT/CT data for patient-specific 3-D dosimetry in radionuclide therapy. Eur. J. Nucl. Med. Mol. Imaging. 2011 Dec. 38 (12) 2173-2185” in which Berker et al use a three dimensional CT image, two planar conjugate-view scintigraphies, and a three dimensional SPECT image as the starting point. The three dimensional SPECT image is acquired from a point in time after the same radiotracer measured in the scintigraphies is administered, and offers a better estimate of the shape of the radiotracer distribution within each compartment. Rather than describing the activity within each compartment as being homogeneous, thus as one basis function wherein all voxels have the same radiotracer activity, each compartment is described by two scaling factors and two basis functions. One basis function represents a homogeneous background voxel radiotracer activity and the other represents a spatially-varying voxel radiotracer activity. The first basis function is equivalent to the single basis function in QPLANAR. This way, each compartment is described by the same set of voxels in which the total activity of any one voxel is determined by the linear sum of a homogeneous voxel activity and the spatially-varying voxel activity. The spatially varying voxel activity represented by the second basis function is derived from the SPECT image which has been acquired from a point in time after the administration of the radiotracer. The SPECT-derived voxel activity represented by the second basis function is normalised to that of the assumed homogeneous activity represented by the first basis function. For each compartment, independent scaling factors are assigned to each basis function and the radiotracer activity distribution within any compartment at any point in time can be estimated by adjusting each of the scaling factors. Each basis function is subsequently projected onto each of the two two-dimensional planes corresponding to the positions of the two-dimensional conjugate view scintigraphies. This results in two projected basis functions per compartment for each of the two scintigraphies. The two projected basis functions per compartment are then rigidly co-registered to their corresponding scintigraphy to assure spatial correspondence between the projection and the scintigraphy. Finally the scaling factors for both the homogeneous radiotracer activity, and for the spatially-varying radiotracer activity are adjusted until a best fit is obtained between the sum of the projected basis functions and the measured scintigraphy. The best fit again yields an approximation to the radiotracer activity in each compartment. By measuring several such scintigraphies over time and fitting the projected activities from each compartment, the desired compartment radiotracer activities can be estimated at the time of each scintigraphy. In so doing a more accurate representation of the activity distribution within the compartment yields more accurate fitted scaling factors and thus a more accurate estimate of the radiotracer activity within each compartment.
However the aforementioned solutions still suffer from the drawback of inaccurately fitting the radiotracer activity within each particular compartment. Consequently they result in a poor estimate of the activity as a function of time in each which can lead to a physician making an imperfect diagnosis or further to poor accuracy in calculating the necessary dose of radioactive therapy agent that is subsequently administered to the body during a radiotherapy treatment stage.